1 MRC Centre for Reproductive Health, University of Edinburgh, UK2 BHF/University Centre for Cardiovascular Science, University of Edinburgh, UK3 MRC Centre for Inflammation Research, University of Edinburgh, UK

Background: Premature babies are particularly vulnerable to brain injury. In this study we focus on cortical brain damage that can result in the long-term cognitive, behavioural, attentional or socialization deficits.
We tested the hypothesis that complement activation plays a role in the cortical brain abnormalities in foetuses born preterm in a mouse model of inflammation-induced preterm labour. We also investigate potential treatments to prevent foetal cortical brain abnormalities and preterm birth.

Methods: We used a mouse model of inflammation-induced preterm birth (PTB) that resembles the spontaneous PTB clinical scenario. We also studied isolated foetal cortical neurons in culture. Non-invasive proton magnetic resonance spectroscopy (1HMRS) was used to study in vivo foetal brain metabolism in uterus. BOLD imaging was used to measure brain oxygenation. We detected complement C3 deposition by MRI in the foetal brains with anti-C3 antibodies conjugated with superparamagnetic iron oxide (SPIO) particles. All mouse studies were conducted in accordance with Home Office welfare and ethical regulations

Conclusion: This study shows that complement activation plays a crucial role in cortical foetal brain injury in PTL and suggests that complement inhibitors and statins might be good therapeutic options to improve neonatal outcomes in preterm birth. Clinical trials should be organized to confirm these studies in humans.